Buccal mucosa porcine permeability

A recent study, however, has shown that aminopeptidase activity is present on the surface of porcine buccal mucosa, and that various aminopeptidase inhibitors, including amastatin and sodium deoxycholate, reduce the mucosal surface degradation of the aminopeptidase substrate, leucine-enkephalin [149], Since the peptidases are present on the surface of the buccal mucosa, they may act as a significant barrier to the permeability of compounds which are substrates for the enzyme. In addition to proteolytic enzymes, there exist some esterases, oxidases, and reductases originating from buccal epithelial cells, as well as phosphatases and carbohydrases present in saliva [154], all of which may potentially be involved in the metabolism of topically applied compounds. 

Recently it has been claimed that the tissue can be considered viable if the drug permeability does not change over the course of the experiment, and thus the actual permeability experiments themselves may provide insight into the viability of the tissue [109, 157], This method was employed in permeation experiments using porcine buccal mucosa, where the permeability of compounds was assessed in two consecutive permeability experiments to ensure the nature of the barrier was not compromised [111, 112]. While this demonstrates that the barrier nature of the tissue was unaltered between the permeation experiments, the tissue may have already undergone tissue death in the time between the excision and the commencement of the initial permeation experiment, and thus the permeability rate obtained in vitro may not be representative of the in vivo situation. Therefore, more studies assessing the dependence of the barrier nature of the buccal mucosa on tissue viability are... 

The buccal mucosa does serve as an alternative route for administering compounds systematically however, to ensure particular compounds are candidates for delivery across this biological tissue, preclinical screening is essential. While in vivo human permeability studies are ideal, due to their costs and associated issues, it is necessary to perform such screening in vitro. Assessment of compound permeability across porcine buccal mucosa has been widely used and can provide the preclinical biopharmaceutical scientist with much information relating to permeability, routes of transport, and effects of various chemical penetration enhancers. 

Jasti BR, Zhou S, Mehta RC, Li X (2000) Permeability of antisense oligonucleotides through porcine buccal mucosa. Int J Pharm 208 35-39... 

Nielsen HM, Rassing MR (2000b) TR146 cells grown on filters as a model of human buccal epithelium IV. Permeability of water, mannitol, testosterone and P-adrenoceptor antagonists. Comparison to human, monkey and porcine buccal mucosa. Int J Pharm 194 155-167... 

Nielsen HM, Rassing MR (2002) Nicotine permeability across the buccal TR146 cell culture model and porcine buccal mucosa in vitro Effect of pH and concentration. Eur J Pharm Sci 16 151-157... 

Senel S, Hoogstraate AJ, Spies F, Verhoef JC, Bos-van Geest A, Junginger HE, Bodde HE (1994) Enhancement of in vitro permeability of porcine buccal mucosa by bile salts Kinetic and histological studies. J Control Release 32 45-56... 

As noted earlier, the choice of species for experimentation is critical due to anatomical differences and it may also reflect species, as well as individual, differences in the expression/activity of transporter and metabolic proteins [43, 44], Since the fraction absorbed across buccal mucosa in vivo is not established for many compounds in different species including humans, the potential existence of a correlation between in vitro permeability coefficients in freshly isolated pig, dog, monkey, and human buccal mucosa was investigated (Figure 7.3). The correlation coefficient obtained for porcine and canine tissue was poor (0.65 and 0.67, respectively, at the 95% confidence level). Results for relatively high permeability compounds in porcine tissue resemble those previously reported where permeability coefficients were by an order of magnitude... 

Van Eyk AD, and Van der Biijl P (2004) Comparative permeability of various chemical markers through human vaginal and buccal mucosa as well as porcine buccal and mouth floor mucosa. Arch. Oral Biol. 49 387-392. 

Agarwal V, Habib W, and Moe D (2005) Effervescent mediated transmucosal enhancement of fentanyl permeability Comparison across ex vivo porcine buccal mucosa and in vitro cultured human buccal epithelium test. American Association Pharm. Sci. Abs. T2126. 

Fatty acid esters would be predicted to have little irritation or toxic effects. Ex vivo permeability studies conducted in porcine buccal mucosa showed significant permeation enhancement of an enkephalin from liquid crystalline phases of glycerine monooleate [32]. These were reported to enhance peptide absorption by a cotransport mechanism. Diethylene glycol monoethyl ether was reported to enhance the permeation of essential oil components of Salvia desoleana through porcine buccal mucosa from a topical microemulsion gel formulation [33]. Some sucrose fatty acid esters, namely, sucrose laurate, sucrose oleate, sucrose palmitate, and sucrose stearate, were investigated on the permeation of lidocaine hydrochloride [34], with 1.5% w/v sucrose laurate showing a 22-fold increase in the enhancement ratio. 

Movement of penetrants across the mucous membranes is by diffusion. At steady state, the amount of a substance crossing the tissue per unit of time is constant and the permeability coefficients are not influenced by the concentration of the solutions or the direction of nonelectrolyte transfer. As in the epidermis of the skin, the pathways of permeation through the epithelial barriers are intercellular rather than intracellular. The permeability can be enhanced by the use surfactants such as sodium lauryl sulfate (a cationic surfactant). An unsaturated fatty acid, oleic acid, in a propylene glycol vehicle can act as a penetration enhancer for diffusion of propranolol through the porcine buccal mucosa in vitro. Delivery of biopharmaceuticals across mucosal surfaces may offer several advantages over injection techniqnes, which include the following ... 

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